We are evaluating the development of serum sickness in humans with the use of various in-depth clinical and immunological analyses. We have evaluated 14 patients with various hematological dyscrasias treated with horse anti-thymocyte globulin (ATG), infused over a 10-28 day course for aplastic anemia and other bone marrow dysfunctions. Twelve of 14 patients developed symptoms of serum sickness usually 10-14 days after the start of ATG infusion. The following organ systems were involved in decreasing frequency: skin, gastrointestinal, rheumatological, reticuloendothelial, and renal. The formation of immune complexes and the consumption of complement closely correlated to the serum sickness symptoms. Treatment with corticosteroids administered concurrently was reflected in fewer symptoms and decreased levels of immune complexes. Hematopoietic recovery did not require preceding serum sickness or immune complex formation.